agmatine

thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
anyone using this? what's your dosing look like? effects?
 

JaredGalloway

Well-known member
Awards
1
  • Established
I am also interested in hearing some feedback on this...
 
kingdong

kingdong

Well-known member
Awards
1
  • Established
I havn't used it. In 2002 I remember picking up one of my brothers fitness magazines, which was probably already old, and readng how it was the next big thing. Now it's 2009. In that article they tried to market it as a test booster. Now it's a pump product with some sort of mental effect.
 
bolt10

bolt10

Well-known member
Awards
2
  • RockStar
  • Established
MAN Blueprint 4 caps immediately upon waking. Stuff is awesome in my experience(just picked up 3 more bottles to run as soon as they arrive).

I notice improved mood, better sleep, better pumps, and a slight leaning out effect. I really enjoy using it and like it due to it being more than just a cosmetic product, due to other added health benefits.
 
bioman

bioman

Well-known member
Awards
1
  • Established
Been eyeing this one but haven't had a chance to buy it.
 
BBB

BBB

Well-known member
Awards
1
  • Established
anyone using this? what's your dosing look like? effects?
I recently finished a bottle of Blue Print by MAN. I took it for 20 days as recommended. I did notice slightly better "pumps" in the gym but other than that I can't say that it did much for me. I'm sure that it has signifigant health benefits but at $3/day it is quite espensive. Since I love the pump, I recently ordered another bottle and I will taking 4 capsules about an hour or so before each workout to see if it inhances the "pump" taken in this manner. If not I will take 4 capsules upon waking only on workout days. Since I workout 3 days a week a bottle should last for about 6-7 weeks used in this manner.

As I said "I love the pump". Thus far the best "pump" I have felt, other than while jucing, is a combination of formestane and AMS Hyper Pump. The pumps from this combination are awsome. I'm not sure if Blue Print can do much to add to this effect.
 
poison

poison

Board Sponsor
Awards
3
  • Established
  • First Up Vote
  • RockStar
I used two bottles. I noticed very few effects, and what effects I did notice were consistant with RALA, and not much more. I was disappointed, as the writeup was well written and in depth, and MAN is a great company.
 
thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
I used two bottles. I noticed very few effects, and what effects I did notice were consistant with RALA, and not much more. I was disappointed, as the writeup was well written and in depth, and MAN is a great company.
i am on 2nd bottle and am noticing increased muscle fullness, leaning out, sensitivity to carbs and prolonged-fuller erections. also feel like i have more endurance and stamina. since i am using BLUE PRINT, i was curious about the bulk agmatine powder that doesn't have the r-ala. but for the price-getting both the agmatine and r-ala, BLUE PRINT seems a much better deal than buying the bulk agmatine.
 
mattikus

mattikus

Well-known member
Awards
1
  • Established
I have used the bulk and blueprint. I still got excellent pumps when adding a gram to whatever pre-workout concoction I was using, and the sense of well being and stamina. The only difference I got was the carb sensitivity and sometimes hypo feeling that came with the RALA. Great stuff, imo, I'm glad you started this thread to remind me of how much I liked it.
 
thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
I have used the bulk and blueprint. I still got excellent pumps when adding a gram to whatever pre-workout concoction I was using, and the sense of well being and stamina. The only difference I got was the carb sensitivity and sometimes hypo feeling that came with the RALA. Great stuff, imo, I'm glad you started this thread to remind me of how much I liked it.
i looked at the bulk agmatine and at BLUE PRINT, for the price of buying both bulk agmatine and bulk r-ala, BLUE PRINT was a no-brainer. i take it you came to same conclusion after trying both?
 
mattikus

mattikus

Well-known member
Awards
1
  • Established
i looked at the bulk agmatine and at BLUE PRINT, for the price of buying both bulk agmatine and bulk r-ala, BLUE PRINT was a no-brainer. i take it you came to same conclusion after trying both?
Yessir, if you want the R-ALA then Blueprint is the way to go.
 

fayd

New member
Awards
0
I used nutra's bulk agmatine for 25 days. What I noticed: dramatically enhanced vascularity, similar to a light cycle. Concurrently, I had improved pumps (not as drastic, though). For one dollar a day though, the positives were not enough to make me a repeat buyer. I would not rule out using MAN bp, however, esp on a discount.
 
UNCnate

UNCnate

Board Sponsor
Awards
1
  • Established
This is a lot of peoples favorite supplement.
 
thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
This is a lot of peoples favorite supplement.
yeah, kind of surpised about the interest. don't hear it mentioned that much.:cheers:
 
SonicSWOLE

SonicSWOLE

Member
Awards
1
  • Established
yeah, kind of surpised about the interest. don't hear it mentioned that much.:cheers:

Yeah, I have been interested for quite a while. I just have yet to pull the trigger.
 
thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
Yeah, I have been interested for quite a while. I just have yet to pull the trigger.
i am really enjoying it. effects seem to get better over time.:cheers:
 
thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
Agmatine inhibits NMDA receptors. I'll pass

More harm than good. Lets all take a supplement that makes us feel good in the gym but ignore everything else it does in the body.
let me check with my buddy on another forum about the nmda inhibition. but he did say that arginine has a feedback loop which agmatine bypasses.:cheers: good looking out natty, let me check on that.
 
thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
Yu, Marcillo, Fairbanks, Wilcox, and Yezierski (2000) promote the
use of agmatine, an NMDA receptor antagonist and nitric oxide synthase (NOS)
inhibitor.
are you saying that agmatine inhibits nitric oxide? i though NO increase was what gave the pump??? i am very confused now.
 
thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
Numerous studies say that agmatine inhibits nitric oxide synthase. Maybe it was the good ol' placebo effect?



Nitric oxide synthase is what converts arginine to NO.


And don't forget that it also inhibits NMDA.



I love the supplement industry lately.
this is a lot to take in. i feel like a 6 year old being told there is no santa claus, lol.
 
HYBRID

HYBRID

Board Sponsor
Awards
1
  • Established
Natty, Can I see those studys if you have a link? Also what serving amount was used iin the study that shows it inhibits NMDA. I have heard of this but only in large servings. Thats why its not reccomended to consume more than 1000-1500 mg per day.

I have also seen numerous studys supporting Nitric Oxide synthesis and its ability to
inhibit Nitric Oxide breakdown so I would like to review. I appreciate it. You can PM me the link if you want.
 
HYBRID

HYBRID

Board Sponsor
Awards
1
  • Established
exactly but there was some concern in a study I read only when supplementing with large amounts. I know Dr Houser was experimenting at one point with large amounts. Ill have to find his post on his experience.

Thanks for the reference Natty. Appreciate it.
 
HYBRID

HYBRID

Board Sponsor
Awards
1
  • Established
Im sorry that you are offended. I respect you opinon as you have everyright to not want to use a product or ingredient. There wsa no intention to persuade you to use or not use Agamatine.
 
BBB

BBB

Well-known member
Awards
1
  • Established
Agmatine inhibits NMDA receptors. I'll pass

More harm than good. Lets all take a supplement that makes us feel good in the gym but ignore everything else it does in the body.
I put a lot of faith in Dr Housers recommendations. He dosen't recommended anything without first doing his research. It's difficult for me to beleive that he would recommend anything that would be harmful.
 
HYBRID

HYBRID

Board Sponsor
Awards
1
  • Established
I understand that. I was just waiting for some guy to post a some dumb study and claim everyone should take his product containing agmatine.

Just because Dr. houser said something doesnt mean much. A lot of doctors are mis-informed and have not spent the right amount of time researching into what they are talking about. Especially primary care physicians. Most of them carry around little PDAs where they read off what prescription you should be taking for your symptoms.

And just to state the facts again... 1 study means nothing. How many times have you read a study about a compound saying it does one thing, then read another saying it doesnt? Its happened to me tons of times.
lol I just saw the extra text you added to this post sorry for the late response. Dr Houser is very reputable as he does his own research before reccomending something. May not be the trusted source for everone and thats fine if its not for you. I dont think in any thread here anyone addressed you directly but your responding as if someone is.

There are a lot more than 1 study brother as I have been researching this ingredient for a while now I have not seen the one that you are refering to thats why I asked as friendly as I could to guide me in the right direction. I dont know who said theres only 1 study maybe your refering to when I said I read a study.

Also your going to find conflicting research in almost anything. Again exactly why Im keeping an open mind and asked for your help to review the studys you have read. Maybe I missed something.
 
andrew732

andrew732

Well-known member
Awards
1
  • Established
Blocking NMDA will cause a blocking effect in the thinking process but to say "brain damage", that is a tad deep, personally PH's are worse for the brain.
 
flightposite

flightposite

Board Sponsor
Awards
1
  • Established
WOW i dont know what think any more lol.
 
HYBRID

HYBRID

Board Sponsor
Awards
1
  • Established
Agmatine inhibits NMDA in your body...naturally..without supplementation. Supplementation only increases it.

Just go on scholar.google.com and google: agmatine nitric oxide synthase -- and -- agmatine nmda
Question for you. If there was a study showing that Agamatine caused no additional threat to inhibiting NMDA in servings of 1000 mg or less would you consider using it? If not based on POSSIBLE increased side effect how do you feel about Agamatine inhibiting NMDA in the body naturally? Must be a serious issue still for you. My point is that everything has a negative effect when consumed in excessive amounts . The reason why I brought up Dr Houser was because he was aware of this and decided to experiment in higher dose. Like I said I don’t know the result. Perhaps someone else can chime in on that. Even if there’s only one study I don’t see why just because there’s only 1 that it should be discredited. This may be an ingredient that needs further research but as you can see from recent users seems to be doing something and IMO leaves me even more curious.
 
strategicmove

strategicmove

Legend
Awards
2
  • Legend!
  • Established
HYBRID

HYBRID

Board Sponsor
Awards
1
  • Established
Yes I have heard great things. I havent tried Agamatine with R-Ala yet. Might give it a go.
 
thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
Yep! Blue Print is awesome.
i am on 2nd bottle and i haven't drove my car into a tree-yet. seriously, i feel like motor skills are improved since starting. as far as cognitive skills well i am kinda dumb to start with so it might be hard to tell a difference.:cheers:
 
HYBRID

HYBRID

Board Sponsor
Awards
1
  • Established
If the study was a real study done on +50 humans from real doctors, not some grad students or sponsored by a nutritional company, then i would consider the study valid if that's what your asking.

Agmatine does what it is supposed to in the body, at the normal levels the body creates. Whether it inhibits NMDA or not in the body, it does what its supposed to.

POSSIBLE NMDA inhibition from a dietary supplement is more than enough to make me not take it.

Sure, most things have negative effects when taken in amounts. But what are those negative effects? Do you know the funtion of NMDA in its entirety? Do you know the function of NMDA inhibition it its entirety? Apparently not, otherwise this wouldnt be of question to you.

Other nutritonal supplements like taking protein too much isnt going to f*** with your NMDA receptors. You will probably just **** it out.

Just one study should not be discredited, but it should not be credited either. That was my point. And again, all of this needs to be taken more seriously since we are talking about the NMDA receptor here. It controls the plasticity of your neurons for crying out loud.
Well shi* I hope your not using your own product Epistane because it is hepatoxic and damaging to lipid levels. Im just saying.... If these concerns are in this product as well than why would you use it? I guess as you say POSSIBLE NMDA inhibition from a dietary supplement is more than enough to make you not take it than I hope your as concerned with your health in regards to Pro Hormones. And no this is not apples and oranges because my base on this post is HEALTH risk not Prohormones vs Agamatine

I have taken Prohormones as well and taken the risk. I can assure you I feel more comfortable using Agamatine.
 
HYBRID

HYBRID

Board Sponsor
Awards
1
  • Established
You're obviously associated with a company selling an agmatine product.

Here's the thing. Most people know prohormones cause heptatoxicity. You're comparing apples to oranges here. The mechanism of steroid molecules are VERY well researched, studied, and understood. I know what heptatoxicity is. I know what it does. I know what Epistane does.

When I take epistane, i know it is affecting my cholesterol levels and my liver enzymes. I am OK with that. It is a choice a make.

Don't try going off on some random epistane tangent. This thread is about Agmatine. It's not about me, or Epistane.

Idk who you are, but you're obviously an alter of a previous member, otherwise you wouldnt know I was associated with IBE.

Are you seriously comparing downgradation of neuron plasticity to heptatoxicity?

Have you ever taken ANY type of neuroscience or neurophysiology class?

Did you pass?
Lol sorry I'm on my phone so this will be short. I know who the ibe reps are here I come to this forum a lot. Also its in your account info not sure if you knew that :) your the one making this about epistane and ibe i just wanted to point out that its a known fact that pro hormones are toxic and bad yet you use it. I guess maybe as you said you know the risk my point was that in lower doses if someone wishes to use agamatine but in your opinion its bad but in normal doses of epistane its toxic without a doubt. So are you willing to sacrifice your health as long as it doesn't affect your ability to function mentaly? I'm not claiming to be a proffessional on the brain and function. Dude all I asked you for was a simple link to your posts so I can further research and you exploded. Again sorry for any spelling or grammer errors.
 
strategicmove

strategicmove

Legend
Awards
2
  • Legend!
  • Established
Just like every other idiotic thread that gets started on this forum, this is my last post in this thread. I stated the facts and the science. Everyone associated with agmatine tried to throw some bull**** back. There's such a low level of education on this board its disgusting. It used to be one of the most educated boards on the internet.

Everyone enjoy their agmatine :)
You always end up insulting others after they challenge your position on any of your so-called "facts and science" posts. If the level of education on this board is disgusting, you either help change it positively (and in a respectful manner) or you stop contributing to the level of disgust by your arrogance! Personally, I do not think there are any "idiotic" threads here, rather specific idiotic responses. What is idiotic about a thread in which someone tries to get the opinion of users of a particular compound, in this case agmatine? Anyone that feels the thread is idiotic can let it be. If this individual decides to contribute in that thread, however, he should be ready for a healthy discussion, based on mutual respect, and should not refer to the others as "idiots" if they do not immediately share his apparently not-so-unshakeable "facts and science".
 
andrew732

andrew732

Well-known member
Awards
1
  • Established
You always end up insulting others after they challenge your position on any of your so-called "facts and science" posts. If the level of education on this board is disgusting, you either help change it positively (and in a respectful manner) or you stop contributing to the level of disgust by your arrogance! Personally, I do not think there are any "idiotic" threads here, rather specific idiotic responses. What is idiotic about a thread in which someone tries to get the opinion of users of a particular compound, in this case agmatine? Anyone that feels the thread is idiotic can let it be. If this individual decides to contribute in that thread, however, he should be ready for a healthy discussion, based on mutual respect, and should not refer to the others as "idiots" if they do not immediately share his apparently not-so-unshakeable "facts and science".
Could not have said better!:cheers:
 
strategicmove

strategicmove

Legend
Awards
2
  • Legend!
  • Established
Could not have said better!:cheers:
AnabolicMinds is founded on the pillars of Learning, Teaching, Leading. I am of the firm conviction that we should keep these principles in mind whenever we post or interact with others on this forum. Nothing more, nothing less.
 
andrew732

andrew732

Well-known member
Awards
1
  • Established
AnabolicMinds is founded on the pillars of Learning, Teaching, Leading. I am of the firm conviction that we should keep these principles in mind whenever we post or interact with others on this forum. Nothing more, nothing less.
AGREE 100%! We all can always learn, there is nothing wrong to state your argument, provide LEGIT reasoning and then answer/comment respectfully, its not hard. Problem is people have too much pride and arrogance and let that tragic flaw get the most out of themselves.
 
strategicmove

strategicmove

Legend
Awards
2
  • Legend!
  • Established
If you are interested, you may read some of the following and make up your own mind. I also encourage you to do your own research. Always helps.


Neuroscience. 2006 Sep 15;141(4):2019-27. Epub 2006 Jun 13.
Neuroprotective effects of agmatine against cell damage caused by glucocorticoids in cultured rat hippocampal neurons.
Zhu MY, Wang WP, Bissette G.

Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. [email protected]
In the present study the neuroprotective effects of agmatine against neuronal damage caused by glucocorticoids were examined in cultured rat hippocampal neurons. Spectrophotometric measurements of lactate dehydrogenase activities, beta-tubulin III immunocytochemical staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling assay (TUNEL) labeling and caspase-3 assays were carried out to detect cell damage or possible involved mechanisms. Our results show that dexamethasone and corticosterone produced a concentration-dependent increase of lactate dehydrogenase release in 12-day hippocampal cultures. Addition of 100 microM agmatine into media prevented the glucocorticoid-induced increase of lactate dehydrogenase release, an effect also shared with the specific N-methyl-D-aspartate receptor antagonist MK801 and glucocorticoid receptor antagonists mifepristone and spironolactone. Arcaine, an analog of agmatine with similar structure as agmatine, also blocked glucocorticoid-induced increase of lactate dehydrogenase release. Spermine and putrescine, the endogenous polyamine and metabolic products of agmatine without the guanidino moiety of agmatine, have no appreciable effect on glucocorticoid-induced injuries, indicating a structural relevance for this neuroprotection. Immunocytochemical staining with beta-tubulin III confirmed the substantial neuronal injuries caused by glucocorticoids and the neuroprotective effects of agmatine against these neuronal injuries. TUNEL labeling demonstrated that agmatine significantly reduced TUNEL-positive cell numbers induced by exposure of cultured neurons to dexamethasone. Moreover, exposure of hippocampal neurons to dexamethasone significantly increased caspase-3 activity, which was inhibited by co-treatment with agmatine. Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from glucocorticoid-induced neurotoxicity, through a possible blockade of the N-methyl-D-aspartate receptor channels or a potential anti-apoptotic property.
Brain Res. 2006 Apr 21;1084(1):210-6. Epub 2006 Mar 20.
Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons.
Wang WP, Iyo AH, Miguel-Hidalgo J, Regunathan S, Zhu MY.

Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, USA.
Agmatine is a polyamine and has been considered as a novel neurotransmitter or neuromodulator in the central nervous system. In the present study, the neuroprotective effect of agmatine against cell damage caused by N-methyl-D-aspartate (NMDA) and glutamate was investigated in cultured rat hippocampal neurons. Lactate dehydrogenase (LDH) activity assay, beta-tubulin III immunocytochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay were conducted to detect cell damage. Exposure of 12-day neuronal cultures of rat hippocampus to NMDA or glutamate for 1 h caused a concentration-dependent neurotoxicity, as indicated by the significant increase in released LDH activities. Addition of 100 microM agmatine into media ablated the neurotoxicity induced by NMDA or glutamate, an effect also produced by the specific NMDA receptor antagonist dizocilpine hydrogen maleate (MK801). Arcaine, an analog of agmatine with similar structure as agmatine, fully prevented the NMDA- or glutamate-induced neuronal damage. Spermine and putrescine, the endogenous polyamine and metabolic products of agmatine without the guanidine moiety of agmatine, failed to show this effect, indicating a structural relevance for this neuroprotection. Immunocytochemical staining and TUNEL assay confirmed the findings in the LDH measurement. That is, agmatine and MK801 markedly attenuated NMDA-induced neuronal death and significantly reduced TUNEL-positive cell numbers induced by exposure of cultured hippocampal neurons to NMDA. Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property.
Neurosci Bull. 2006 May;22(3):187-91.
Neuroprotective effects of receptor imidazoline 2 and its endogenous ligand agmatine.
Qiu WW, Zheng RY.

Department of Neurology, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China; E-mail: [email protected].
Receptor imidazoline 2 (I(2)) is one of the imidazoline receptors with high affinity for [(3)H]-idazoxan. Receptor I(2), being classified into I(2A) and I(2B) subtypes, is mainly localized to the outer membrane of mitochondria in liver, kidney and brain. Receptor I(2), displaying high similarity of sequence with monoamine oxidase-B (MAO-B), is structurally related to MAO-B, but the I(2) imidazoline binding site (I(2)BS) with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I(2). Accumulating evidence have revealed that the activation of receptors I(2) may produce neuroprotective effects by increasing expression of glial fibrillary acidic protein (GFAP) in astrocytes, inhibiting activity of MAO, reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia, injury, glutamate-induced neurotoxicity by activating imidazoline receptors, blocking N-methyl-D-aspartate (NMDA) receptor, inhibiting all isoforms of nitric oxide synthase (NOS), and selectively blocking the voltage-gated calcium channels (VGCC). It would be expected that agmatine is one of the potential neuroprotective agents.
Trends Pharmacol Sci. 2000 May;21(5):187-93.
Is agmatine a novel neurotransmitter in brain?
Reis DJ, Regunathan S.

Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 411 East 69th Street, KB410, New York, NY 10021, USA. [email protected]
Recent evidence suggests that agmatine, which is an intermediate in polyamine biosynthesis, might be an important neurotransmitter in mammals. Agmatine is synthesized in the brain, stored in synaptic vesicles in regionally selective neurons, accumulated by uptake, released by depolarization, and inactivated by agmatinase. Agmatine binds to alpha2-adrenoceptors and imidazoline binding sites, and blocks NMDA receptor channels and other ligand-gated cationic channels. Furthermore, agmatine inhibits nitric oxide synthase, and induces the release of some peptide hormones. As a result of its ability to inhibit both hyperalgesia and tolerance to, and withdrawal from, morphine, and its neuroprotective activity, agmatine has potential as a treatment of chronic pain, addictive states and brain injury.
J Am Soc Nephrol. 2000 Dec;11(12):2256-64.
Agmatine inhibits cell proliferation and improves renal function in anti-thy-1 glomerulonephritis.
Ishizuka S, Cunard R, Poucell-Hatton S, Wead L, Lortie M, Thomson SC, Gabbai FB, Satriano J, Blantz RC.

Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
Changes in the expression of alternate arginine metabolic pathways have been implicated in the pathogenesis of experimental glomerulonephritis. Agmatine, decarboxylated arginine, has been shown in vitro to suppress both inducible nitric oxide synthase and the rate-limiting enzyme of polyamine biosynthesis, ornithine decarboxylase (ODC). This study was undertaken to determine whether agmatine administration could reduce tissue injury by decreasing nitric oxide, and reduce cell proliferation, by diminishing ODC activity, in experimental mesangial proliferative glomerulonephritis (Thy-1 nephritis). Agmatine treatment (50 mg/kg per d intraperitoneally) in Thy-1 nephritis rats prevented a reduction in GFR at day 1. Agmatine treatment decreased nitric oxide production in Thy-1 nephritis rats by 23% and 41% at days 1 and 4, respectively. Agmatine treatment also reduced ODC activity and glomerular (3)H-thymidine incorporation on days 1, 4, and 7. Histologic evaluation revealed a decline in mesangial cell proliferation and extracellular matrix accumulation associated with agmatine treatment administered before or 24 h after Thy-1 antibody, and this was confirmed by a reduction in the number of cells expressing proliferating cell nuclear antigen on days 4 and 7. These studies provide the first in vivo evidence that agmatine administration can reduce cellular proliferation in Thy-1 nephritis and attenuate the initial reduction in renal function associated with this model.
Acta Physiol Scand. 2000 Jan;168(1):21-5.
Biological effects of arginine metabolites.
Blantz RC, Satriano J, Gabbai F, Kelly C.

University of California, San Diego, California 92161, USA.
Arginine and its metabolites exert physiological effects on the vasculature and on the kidney and also provide important influences on the regulation of cell proliferation. We summarize the known information regarding two major metabolites of arginine: (a) nitric oxide (NO) and (b) agmatine, decarboxylated arginine. Both agents appear to interact in producing vasodilation and increases in glomerular filtration rate (GFR) in the kidney. There is evidence for inter-regulation of arginine pathways in the sense that agmatine is capable of inhibiting inducible nitric oxide synthase (iNOS), the inflammatory NOS isoform. Both NO and agmatine influence cell proliferation via effects on polyamine synthesis. In addition, both NO and agmatine exert inhibitory effects on ornithine decarboxylase (ODC) and the putrescine transporter by significantly different mechanisms. Therefore, arginine and arginine metabolites exert both vascular regulatory functions and impact on the regulation of cell proliferation. Significant inter-regulation among arginine pathways occurs within the three metabolic major pathways within the cell: (1) nitric oxide synthase (2) arginase and ornithine decarboxylase, and (3) arginine decarboxylase.
Ann N Y Acad Sci. 2003 Dec;1009:34-43.
Agmatine: at the crossroads of the arginine pathways.
Satriano J.

University of California, San Diego, Department of Medicine, Division of Nephrology-Hypertension, San Diego, California 92161, USA. [email protected]
In acute inflammatory responses, such as wound healing and glomerulonephritis, arginine is the precursor for production of the cytostatic molecule nitric oxide (NO) and the pro-proliferative polyamines. NO is an early phase response whereas increased generation of polyamines is requisite for the later, repair phase response. The temporal switch of arginine as a substrate for the inducible nitric oxide synthase (iNOS)/NO axis to arginase/ornithine decarboxylase (ODC)/polyamine axis is subject to regulation by inflammatory cytokines as well as interregulation by the arginine metabolites themselves. Herein we describe the capacity of another arginine pathway, the metabolism of arginine to agmatine by arginine decarboxylase (ADC), to aid in this interregulation. Agmatine is an antiproliferative molecule due to its suppressive effects on intracellular polyamine levels, whereas the aldehyde metabolite of agmatine is a potent inhibitor of iNOS. We propose that the catabolism of agmatine to its aldehyde metabolite may act as a gating mechanism at the transition from the iNOS/NO axis to the arginase/ODC/polyamine axis. Thus, agmatine has the potential to serve in the coordination of the early and repair phase pathways of arginine in inflammation.

Brain Res. 2000 Jul 28;872(1-2):141-8.
Agmatine suppresses nitric oxide production in microglia.
Abe K, Abe Y, Saito H.

Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Tokyo, Japan. [email protected]
We investigated the effect of agmatine, an arginine metabolite synthesized in the brain, in cultured microglia obtained from neonatal rat cerebral cortex. Agmatine (1-300 microM) did not affect viability of cultured microglia. Activation of microglia by lipopolysaccharide (LPS, 1 microg/ml) caused the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) assessed as the accumulation of nitrite in the culture supernatants. Agmatine had no effect on the expression of iNOS, but significantly suppressed the LPS-induced NO production in a concentration-dependent manner. Agmatine was also effective in suppressing the production of NO induced by a combination of interferon-gamma (500 U/ml) and amyloid beta protein (10 microM). In co-cultures of rat cortical neurons and microglia, LPS caused significant loss of neuron viability. The LPS neurotoxicity was not observed in the absence of microglia, and was completely blocked by the NOS inhibitor diphenyleneiodoium chloride. The neuronal death induced by microglia-derived NO was significantly attenuated by the presence of agmatine. These results suggest that agmatine works to protect neurons by inhibiting the production of NO in microglia.
AAPS J. 2006 Jul 21;8(3):E479-84.
Agmatine: biological role and therapeutic potentials in morphine analgesia and dependence.
Regunathan S.

Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, USA. [email protected]
Agmatine is an amine that is formed by decarboxylation of L-arginine by the enzyme arginine decarboxylase (ADC) and hydrolyzed by the enzyme agmatinase to putrescine. Agmatine binds to several target receptors in the brain and has been proposed as a novel neuromodulator. In animal studies, agmatine potentiated morphine analgesia and reduced dependence/withdrawal. While the exact mechanism is not clear, the interactions with N-methyl-D-aspartate (NMDA) receptors, alpha2-adrenergic receptors, and intracellular cyclic adenosine monophosphate (cAMP) signaling have been proposed as possible targets. Like other monoamine transmitter molecules, agmatine is rapidly metabolized in the periphery and has poor penetration into the brain, which limits the use of agmatine itself as a therapeutic agent. However, the development of agmatinase inhibitors will offer a useful method to increase endogenous agmatine in the brain as a possible therapeutic approach to potentiate morphine analgesia and reduce dependence/withdrawal. This review provides a succinct discussion of the biological role/therapeutic potential of agmatine during morphine exposure/pain modulation, with an extensive amount of literature cited for further details.
CNS Drugs. 2007;21(11):885-900.
Agmatine : metabolic pathway and spectrum of activity in brain.
Halaris A, Plietz J.

Department of Psychiatry and Behavioral Neurosciences, Loyola University Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA. [email protected]
Agmatine is an endogenous neuromodulator that, based on animal studies, has the potential for new drug development. As an endogenous aminoguanidine compound (1-amino-4-guanidinobutane), it is structurally unique compared with other monoamines. Agmatine was long thought to be synthesised only in lower life forms, until its biosynthetic pathway (decarboxylation of arginine) was described in the mammalian brain in 1994. Human arginine decarboxylase has been cloned and shown to have 48% identity to ornithine decarboxylase. In neurons of the brain and spinal cord, agmatine is packaged into synaptic vesicles and released upon neuronal depolarisation. Other evidence of a neuromodulation role for agmatine is the presence of a specific cellular uptake mechanism and a specific metabolic enzyme (agmatinase; which forms putrescine).Initially, agmatine was conceptualised as an endogenous clonidine-displacing substance of imidazoline receptors; however, it has now been established to have affinity for several transmembrane receptors, such as alpha(2)-adrenergic, imidazoline I(1) and glutamatergic NMDA receptors. In addition to activity at these receptors, agmatine irreversibly inhibits neuronal nitric oxide synthase and downregulates inducible nitric oxide synthase. Endogenous agmatine is induced in response to stress and/or inflammation. Stressful conditions that induce agmatine include hypoxic-ischaemia and cold-restraint stress of ulcerogenic proportion. Induction of agmatine in the brain seems to occur in astrocytes, although neurons also synthesise agmatine. The effects of injected agmatine in animals include anticonvulsant-, antineurotoxic- and antidepressant-like actions. Intraperitoneal or intracerebroventricular injections of agmatine rapidly elicit antidepressant-like behavioural changes in the rodent forced swim test and tail suspension test. Intraperitoneal injections of agmatine into rats and mice also elicit acute anxiolytic-like behavioural changes in the elevated plus-maze stress test. In an animal model of acute stress disorder, intraperitoneal agmatine injections diminish contextual fear learning. Furthermore, intraperitoneal injections of agmatine reduce alcohol and opioid dependence by diminishing behaviour in a rat conditioned place preference paradigm. Based on these findings, agmatine appears to be an endogenous neuromodulator of mental stress. The possible roles and/or beneficial effects of agmatine in stress-related disorders, such as depression, anxiety and post-traumatic stress disorder, merit further investigation.
 
strategicmove

strategicmove

Legend
Awards
2
  • Legend!
  • Established
.....

Ann N Y Acad Sci. 1999 Jun 21;881:65-80.
Agmatine: an endogenous ligand at imidazoline receptors is a novel neurotransmitter.
Reis DJ, Regunathan S.

Division of Neurobiology, Cornell University Medical College, New York, New York 10021, USA. [email protected]
Agmatine, an amine and organic cation, is an endogenous ligand at alpha 2-adrenergic and imidazoline (I-) receptors, to which it binds with high affinity. In addition, agmatine has properties of an endogenous neurotransmitter. Thus, agmatine (a) is locally synthesized in brain by a specific enzyme, arginine decarboxylase; (b) is stored in a large number of neurons with selective distribution in the CNS; (c) is associated with small vesicles in axon terminals that, at least in hippocampus, make synaptic asymmetric (excitatory) synapses on pyramidal cells; (d) is released from synaptosomes in a Ca(2+)-dependent manner; (e) can be enzymatically degraded by agmatinase in synaptosomes; (f) can be inactivated by selective reuptake; (g) blocks the ligand-gated NMDA receptor channel at sites distinct from ligand-binding and polyamine sites; and (h) has systemic actions when administered intraventricularly. Additionally, (i) agmatine is a precursor of brain putrescine and, hence, of higher polyamines, and (j) it competitively inhibits the activity of all isozymes of nitric oxide synthase. Agmatine meets most criteria to establish it as a novel neurotransmitter/neuromodulator in the CNS. However, agmatine differs from forms of clonidine displacing system with respect to distribution, bioactivity, and capacity to interact with antibodies raised to imidazoline-like drugs. Thus, there are multiple endogenous ligands of the imidazoline receptors, one of which is agmatine.
Neurosci Lett. 2003 Mar 13;339(1):88-90.
Systemic agmatine attenuates tactile allodynia in two experimental neuropathic pain models in rats.
Karadag HC, Ulugol A, Tamer M, Ipci Y, Dokmeci I.

Department of Pharmacology, Faculty of Medicine, Trakya University, 22030-, Edirne, Turkey. [email protected]
Recent evidence suggests that agmatine, an endogenous polyamine metabolite, might be an important neurotransmitter in central nervous system and has potential as a treatment of pain. The aim of our study was to evaluate the effect of agmatine on allodynia in two experimental neuropathic pain models, the spinal nerve ligation (SNL) model and the streptozocin (STZ)-induced diabetic neuropathy in rats, and to determine if the N-methyl-D-aspartate (NMDA) receptor antagonists and the nitric oxide synthase (NOS) inhibitors influence this effect of agmatine. Nerve injury was produced by tight ligation of the left L5 and L6 spinal nerves, and diabetic neuropathy is induced with the injection of a single dose of STZ; these procedures resulted in tactile allodynia in the hindpaw. Tactile allodynia was detected by application of von Frey filaments to the plantar surface of the foot. Agmatine reduced mechanical allodynia with its higher doses. Dizocilpine maleate (MK-801), a NMDA receptor antagonist, and the NOS inhibitors, N(G)-nitro-L-arginine methyl ester and 7-nitroindazole, did not influence the antiallodynic effect of agmatine. These results suggest that agmatine has an antiallodynic effect in both spinal nerve ligation and diabetic models and may be a promising drug in the treatment of neuropathic pain.

J Pharmacol Exp Ther. 2007 Sep;322(3):1237-45. Epub 2007 Jun 5.
Agmatine induces antihyperalgesic effects in diabetic rats and a superadditive interaction with R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid, a N-methyl-D-aspartate-receptor antagonist.
Courteix C, Privat AM, Pélissier T, Hernandez A, Eschalier A, Fialip J.

INSERM, U766, F-63001 Clermont-Ferrand, France. [email protected]
Agmatine, an endogenous cationic amine resulting from the decarboxylation of L-arginine, produces antihyperalgesic and antiallodynic effects in animal models of chronic neuropathic and inflammatory pain. We examined the effect of agmatine on tactile and thermal allodynia and on mechanical hyperalgesia in streptozocin-induced diabetic rats. To determine its mechanism of action and the potential interest of some of its combinations, the antihyperalgesic effect of agmatine was challenged with alpha(2)-adrenergic imidazoline and opioid-receptor antagonists, and its interaction with the opioid-receptor agonist morphine, the competitive N-methyl-D-aspartate receptor antagonist D-CPP [R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid], and the nitric-oxide synthase inhibitor L-NAME (L-N(G)-nitro-L-arginine methyl ester) were examined. When intrathecally (i.t.) injected (4.4 to 438 nmol/rat), agmatine was ineffective in normal rats but suppressed tactile allodynia (von Frey hair test), thermal allodynia (tail immersion test), and mechanical hyperalgesia (paw-pressure test) in diabetic rats. This spinal antihyperalgesic effect was suppressed by idazoxan (40 micromol/rat i.t.) but not by yohimbine (40 micromol/rat i.t.) or naloxone (0.69 micromol/rat i.v.). In diabetic rats, an isobolographic analysis showed that combinations of i.t. agmatine with i.v. L-NAME or with i.t. morphine resulted in an additive antihyperalgesic effect, whereas the agmatine/D-CPP i.t. combination was superadditive. In summary, the present findings reveal that spinal agmatine produces antiallodynic and antihyperalgesic effects in diabetic neuropathic pain involving, at least for its antihyperalgesic effect, the imidazoline receptors. Moreover, agmatine combined with D-CPP produces an antinociceptive synergy in experimental neuropathy, opening opportunities in the development of new strategies for pain therapy.
Eur J Neurosci. 2008 Mar;27(6):1320-32.
Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain.
Zhu MY, Wang WP, Cai ZW, Regunathan S, Ordway G.

Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37604, USA. [email protected]
Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with beta-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress.
Ann N Y Acad Sci. 2003 Dec;1009:127-32.
Is agmatine an endogenous factor against stress?
Aricioglu F, Regunathan S, Piletz JE.

Department of Pharmacology, Faculty of Pharmacy, Marmara University, Haydarpasa, Istanbul, Turkey. [email protected]
Agmatine is an endogenous amine synthesized from the decarboxylation of arginine. A proposed intracellular role of agmatine is to balance the production of polyamines (a promitotic process) and nitric oxide (an inflammatory process). Agmatine is also released from neurons upon depolarization. We previously reported that agmatine concentrations are increased in rat pups' brains shortly after hypoxic-ischemia and in the plasma of depressed patients. Herein, male rats (270-290 g) were divided into four groups receiving different degrees of known stress: 2-hour restraint at 21 degrees C, 4-hour restraint at 21 degrees C, 4-hour restraint at 4 degrees C, and control rats only handled at 21 degrees C. Cortex, cerebellum, medulla, hippocampus, hypothalamus, and blood plasma samples were collected for determination of endogenous agmatine levels. No changes in agmatine levels were detected after 2-hour and 4-hour restraint at room temperature, but concentrations of agmatine were increased in all brain regions except cerebellum after 4-hour restraint in the cold. Plasma agmatine levels (ng/mL) were 6.8 +/- 0.6 in controls versus 58.1 +/- 12.8 in the 4-hour restraint-plus-cold group. Cortical agmatine levels (ng/g wet tissue) were 15.3 +/- 2.4 in controls versus 57.4 +/- 19.6 in the 4-hour restraint-plus-cold group. Therefore, endogenous agmatine was increased in response to cold-restraint stress, possibly as a neuroprotective agent.
Science. 1994 Feb 18;263(5149):966-9.
Agmatine: an endogenous clonidine-displacing substance in the brain.
Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ.

Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.
Comment in:

Science. 1994 Oct 21;266(5184):462-4.
Clonidine, an antihypertensive drug, binds to alpha 2-adrenergic and imidazoline receptors. The endogenous ligand for imidazoline receptors may be a clonidine-displacing substance, a small molecule isolated from bovine brain. This clonidine-displacing substance was purified and determined by mass spectroscopy to be agmatine (decarboxylated arginine), heretofore not detected in brain. Agmatine binds to alpha 2-adrenergic and imidazoline receptors and stimulates release of catecholamines from adrenal chromaffin cells. Its biosynthetic enzyme, arginine decarboxylase, is present in brain. Agmatine, locally synthesized, is an endogenous agonist at imidazoline receptors, a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter.
Br J Pharmacol. 2002 Mar;135(5):1152-8.
Effect of agmatine on locus coeruleus neuron activity: possible involvement of nitric oxide.
Ruiz-Durántez E, Ruiz-Ortega JA, Pineda J, Ugedo L.

Departamento de Farmacología, Facultad de Medicina, Universidad del País Vasco, E-48940 Leioa, Vizcaya, Spain.
1. To investigate whether agmatine (the proposed endogenous ligand for imidazoline receptors) controls locus coeruleus neuron activity and to elucidate its mechanism of action, we used single-unit extracellular recording techniques in anaesthetized rats. 2. Agmatine (10, 20 and 40 microg, i.c.v.) increased in a dose-related manner the firing rate of locus coeruleus neurons (maximal increase: 95 +/- 13% at 40 microg). 3. I(1)-imidazoline receptor ligands stimulate locus coeruleus neuron activity through an indirect mechanism originated in the paragigantocellularis nucleus via excitatory amino acids. However, neither electrolytic lesions of the paragigantocellularis nucleus nor pretreatment with the excitatory amino acid antagonist kynurenic acid (1 micromol, i.c.v.) modified agmatine effect (10 microg, i.c.v.). 4. After agmatine administration (20 microg, i.c.v.), dose-response curves for the effect of clonidine (0.625 - 10 microg kg(-1) i.v.) or morphine (0.3 - 4.8 mg kg(-1) i.v.) on locus coeruleus neurons were not different from those obtained in the control groups. 5. Pretreatment with the nitric oxide synthase inhibitors N(omega)-nitro-L-arginine (10 microg, i.c.v.) or N(omega)-nitro-L-arginine methyl ester (100 microg, i.c.v.) but not with the less active stereoisomer N(omega)-nitro-D-arginine methyl ester (100 microg, i.c.v.) completely blocked agmatine effect (10 and 40 microg, i.c.v.). 6. Similarly, when agmatine (20 pmoles) was applied into the locus coeruleus there was an increase that was blocked by N(omega)-nitro-L-arginine methyl ester (100 microg, i.c.v.) in the firing rate of the locus coeruleus neurons (maximal increase 53 +/- 11% and 14 +/- 10% before and after nitric oxide synthase inhibition, respectively). 7. This study demonstrates that agmatine stimulates the firing rate of locus coeruleus neurons via a nitric oxide synthase-dependent mechanism located in this nucleus.

AAPS J. 2006 Jul 21;8(3):E479-84.
Agmatine: biological role and therapeutic potentials in morphine analgesia and dependence.
Regunathan S.

Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, USA. [email protected]
Agmatine is an amine that is formed by decarboxylation of L-arginine by the enzyme arginine decarboxylase (ADC) and hydrolyzed by the enzyme agmatinase to putrescine. Agmatine binds to several target receptors in the brain and has been proposed as a novel neuromodulator. In animal studies, agmatine potentiated morphine analgesia and reduced dependence/withdrawal. While the exact mechanism is not clear, the interactions with N-methyl-D-aspartate (NMDA) receptors, alpha2-adrenergic receptors, and intracellular cyclic adenosine monophosphate (cAMP) signaling have been proposed as possible targets. Like other monoamine transmitter molecules, agmatine is rapidly metabolized in the periphery and has poor penetration into the brain, which limits the use of agmatine itself as a therapeutic agent. However, the development of agmatinase inhibitors will offer a useful method to increase endogenous agmatine in the brain as a possible therapeutic approach to potentiate morphine analgesia and reduce dependence/withdrawal. This review provides a succinct discussion of the biological role/therapeutic potential of agmatine during morphine exposure/pain modulation, with an extensive amount of literature cited for further details.





Amino Acids. 2004 Jul;26(4):321-9. Epub 2004 Apr 8.
Arginine pathways and the inflammatory response: interregulation of nitric oxide and polyamines: review article.
Satriano J.

Department of Medicine, Division of Nephrology-Hypertension, University of California, San Diego, California, USA. [email protected]
An early response to an acute inflammatory insult, such as wound healing or experimental glomerulonephritis, is the conversion of arginine to the cytostatic molecule nitric oxide (NO). This 'anti-bacterial' phase is followed by the conversion of arginine to ornithine, which is the precursor for the pro-proliferative polyamines as well as proline for the production of extracellular matrix. This latter, pro-growth phase constitutes a 'repair' phase response. The temporal switch of arginine as a substrate for the cytostatic iNOS/NO axis to the pro-growth arginase/ ornithine/polyamine and proline axis is subject to regulation by inflammatory cytokines as well as interregulation by the arginine metabolites themselves. Arginine is also the precursor for another biogenic amine, agmatine. Here we describe the capacity of these three arginine pathways to interregulate, and propose a model whereby agmatine has the potential to serve in the coordination of the early and repair phase pathways of arginine in the inflammatory response by acting as a gating mechanism at the transition from the iNOS/NO axis to the arginase/ODC/polyamine axis. Due to the pathophysiologic and therapeutic potential, we will further examine the antiproliferative effects of agmatine on the polyamine pathway.


Cardiovasc Drug Rev. 2004 Spring;22(1):7-16.
Agmatine signaling: odds and threads.
Berkels R, Taubert D, Gründemann D, Schömig E.

Institut für Pharmakologie, Klinikum der Universität zu Köln, Gleueler Str. 24, D-50931 Köln, Germany. [email protected].
Agmatine is a metabolite of L-arginine. It is formed by the decarboxylation of L-arginine via arginine decarboxylase in bacteria, plants and mammals. It is becoming clear that it has multiple physiological functions as a potential transmitter. Agmatine binds to alpha2-adrenoceptors and to imidazoline binding sites. It blocks NMDA receptors and other ligand-gated cation channels. It also inhibits nitric oxide synthase, induces release of peptide hormones and antizyme and plays a role during cell proliferation by interacting with the generation and transport of polyamines. Although the precise function of endogenously released agmatine is presently still unclear, this review will summarize several aspects concerning the biological function of agmatine.
 
strategicmove

strategicmove

Legend
Awards
2
  • Legend!
  • Established
This selection is non-exhaustive. Do your own research and form your own opinion...

Pharmacol Res. 2004 May;49(5):397-414.
Vascular regulation by the L-arginine metabolites, nitric oxide and agmatine.
Raghavan SA, Dik**** M.

Central Drug Research Institute, Lucknow 226001, U.P., India.
Research on the biochemistry and physiology of l-arginine has remained an attractive area for scientists over the last 100 years due to its diverse physiological functions in mammals. Research on l-arginine was boosted after the identification of nitric oxide (NO) and agmatine and their physiological importance. NO directly modulates ion channels, activates soluble guanylyl cyclase and other important proteins by ADP ribosylation and nitrosylation and binding to heme or iron-sulfur clusters. These modifications and interaction with heme might activate or inhibit various protein kinases, phosphatases and modulate transcription of various nuclear factors to possibly cause cardiovascular diseases like hypertension, ischemia, diabetes, atherosclerosis and angiogenesis. Agmatine holds the key to prevent the toxic effects associated with induction of NO synthesis by its ability to inhibit inducible nitric oxide synthase (iNOS). Agmatine is also synthesized from l-arginine by the enzyme arginine decarboxylase and displays a significant potential in cardiovascular system. Agmatine, with the myriad of effects on calcium homeostasis, seems to modulate various functions in the heart, brain and vasculature. The present review compiles the recent development to improve the understanding the role played by l-arginine-metabolic pathways in cardiovascular system. Though l-arginine and its metabolites are well known to affect various cardiovascular physiologies, the currently available literature is still not sufficient to validate the prophylactic/therapeutic efficacy of l-arginine. l-Arginine and its metabolites, NO and agmatine still hold the key for future research in cardiovascular system.
Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10584-9.
Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.
Fairbanks CA, Schreiber KL, Brewer KL, Yu CG, Stone LS, Kitto KF, Nguyen HO, Grocholski BM, Shoeman DW, Kehl LJ, Regunathan S, Reis DJ, Yezierski RP, Wilcox GL.

Departments of Pharmacology and Neuroscience and Oral Science, University of Minnesota, Minneapolis, MN 55455, USA.
Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury.
Eur J Pharmacol. 2001 Oct 19;429(1-3):23-37.
Pathobiology of neuropathic pain.
Zimmermann M.

Neuroscience and Pain Research Institute, Berliner Strasse 14, 69120 Heidelberg, Germany. [email protected]
This review deals with physiological and biological mechanisms of neuropathic pain, that is, pain induced by injury or disease of the nervous system. Animal models of neuropathic pain mostly use injury to a peripheral nerve, therefore, our focus is on results from nerve injury models. To make sure that the nerve injury models are related to pain, the behavior was assessed of animals following nerve injury, i.e. partial/total nerve transection/ligation or chronic nerve constriction. The following behaviors observed in such animals are considered to indicate pain: (a) autotomy, i.e. self-attack, assessed by counting the number of wounds implied, (b) hyperalgesia, i.e. strong withdrawal responses to a moderate heat stimulus, (c) allodynia, i.e. withdrawal in response to non-noxious tactile or cold stimuli. These behavioral parameters have been exploited to study the pharmacology and modulation of neuropathic pain. Nerve fibers develop abnormal ectopic excitability at or near the site of nerve injury. The mechanisms include unusual distributions of Na(+) channels, as well as abnormal responses to endogenous pain producing substances and cytokines such as tumor necrosis factor alpha (TNF-alpha). Persistent abnormal excitability of sensory nerve endings in a neuroma is considered a mechanism of stump pain after amputation. Any local nerve injury tends to spread to distant parts of the peripheral and central nervous system. This includes erratic mechano-sensitivity along the injured nerve including the cell bodies in the dorsal root ganglion (DRG) as well as ongoing activity in the dorsal horn. The spread of pathophysiology includes upregulation of nitric oxide synthase (NOS) in axotomized neurons, deafferentation hypersensitivity of spinal neurons following afferent cell death, long-term potentiation (LTP) of spinal synaptic transmission and attenuation of central pain inhibitory mechanisms. In particular, the efficacy of opioids at the spinal level is much decreased following nerve injury. Repeated or prolonged noxious stimulation and the persistent abnormal input following nerve injury activate a number of intracellular second messenger systems, implying phosphorylation by protein kinases, particularly protein kinase C (PKC). Intracellular signal cascades result in immediate early gene (IEG) induction which is considered as the overture of a widespread change in protein synthesis, a general basis for nervous system plasticity. Although these processes of increasing nervous system excitability may be considered as a strategy to compensate functional deficits following nerve injury, its by-product is widespread nervous system sensitization resulting in pain and hyperalgesia. An important sequela of nerve injury and other nervous system diseases such as virus attack is apoptosis of neurons in the peripheral and central nervous system. Apoptosis seems to induce neuronal sensitization and loss of inhibitory systems, and these irreversible processes might be in common to nervous system damage by brain trauma or ischemia as well as neuropathic pain. The cellular pathobiology including apoptosis suggests future strategies against neuropathic pain that emphasize preventive aspects.
Neurosci Lett. 2005 Sep 16;385(3):179-83.
Experiments with nitric oxide synthase inhibitors in spinal nerve ligated rats provide no evidence of a role for nitric oxide in neuropathic mechanical allodynia.
Lee DH, Singh JP, Lodge D.

Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. [email protected]
We have investigated the effect of treatment with N(omega)-nitro-l-arginine methylester (l-NAME), a non-selective nitric oxide synthase inhibitor (NOS), both before and after the induction of mechanical allodynia by tight ligation of the left L5 and L6 spinal nerves in rats (SNL rats). The degree of mechanical allodynia was measured by tactile threshold for paw flinching with von Frey filaments. Intraperitoneal (i.p.) administration of l-NAME (3-30 mg/kg) 1 week after the spinal nerve ligation produced a dose-dependent reduction of the behavioral signs of mechanical allodynia, but the effect was not reversed by pretreatment with l-arginine (300 mg/kg). N(omega)-Nitro-l-arginine (l-NNA, i.p., 30 mg/kg), aminoguanidine (AG, i.p., 30 mg/kg) and a potent neuronal NOS inhibitor (LY457963, i.p., 30 mg/kg) did not reduce mechanical sensitivity in the SNL rats. Furthermore, using an ex vivo NOS activity assay, l-NAME partially inhibited the spinal NOS activity, whereas LY457963 almost completely inhibited the spinal NOS activity. Prior administration of l-NAME (i.p., 30 mg/kg) or of MK-801 (0.5 mg/kg), an NMDA antagonist, 30 min before the spinal nerve ligation significantly prevented the development of mechanical allodynia after spinal nerve ligation for an extended period of time. High doses of l-arginine (100 mg/kg or 300 mg/kg, i.p.), however, did not reverse the preemptive effect of l-NAME. These results suggest that neither the anti-allodynic nor the preemptive effects of l-NAME are mediated by NOS inhibition.

Brain Res. 1998 Jun 15;796(1-2):176-86.
Excitatory action of N-methyl-D-aspartate on the rat locus coeruleus is mediated by nitric oxide: an in vivo voltammetric study.
Hall S, Milne B, Jhamandas K.

Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Biochemical, electrophysiological and behavioural studies have provided evidence that activation of N-methyl-D-aspartate (NMDA) receptors contributes to the hyperactivity of noradrenergic neurons of the locus coeruleus (LC) in precipitated opioid withdrawal. Recently, it was demonstrated that central administration of nitric oxide (NO) synthase inhibitors suppresses this hyperactivity suggesting that NO mediates the NMDA receptor activation of LC in opioid withdrawal. Using a combination of microdialysis and in vivo voltammetry, this study examined whether local application of NMDA to the LC in opioid naive animals mimics the NO-dependent LC response seen in opioid withdrawal. In the urethane anaesthetized rat, perfusion of the LC (2 microliters min-1) with a solution of NMDA (5 mmol) via a microdialysis probe for 9 min resulted in a rapid and robust increase (290.1 +/- 32.2% above baseline) in the catechol oxidation current (CA.OC) recorded from the LC using differential normal pulse voltammetry (DNPV). The NMDA microdialysis also produced a large increase in the blood pressure (150.4 +/- 6.9% above baseline). An injection of the non-competitive NMDA receptor antagonist (+)MK-801 (0.5 mg kg-1 i.v.), given 45 min after the start of NMDA application, rapidly returned both the CA.OC signal and the blood pressure response to baseline levels. Pretreatment of animals with intraventricular nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) (100 micrograms) significantly inhibited NOS activity in the LC, PAG-PVG and cerebellum. This dose of L-NAME, administered prior to application of NMDA by microdialysis abolished the NMDA-induced rise in the CA.OC recorded in the LC and the increase in systolic blood pressure. The results show that in voltammetry experiments, NMDA produces hyperactivity of LC and hypertension, responses that are dependent upon the synthesis of NO. Thus, in opioid naive rats, regional NMDA application via microdialysis mimics characteristics of the LC response that occur during the antagonist-precipitated opioid withdrawal.
And so on....
 
thebigt

thebigt

Legend
Awards
6
  • Best Answer
  • The BigT Award
  • Established
  • Legend!
  • RockStar
  • First Up Vote
thanks, strat!!! sorry if i am an idiot for posting a thread on agmatine, but my results so far are very good. i like blue print, and am enjoying the results. wow-after reading your articles i feel smarter already.:cheers:
 
HYBRID

HYBRID

Board Sponsor
Awards
1
  • Established
You always end up insulting others after they challenge your position on any of your so-called "facts and science" posts. If the level of education on this board is disgusting, you either help change it positively (and in a respectful manner) or you stop contributing to the level of disgust by your arrogance! Personally, I do not think there are any "idiotic" threads here, rather specific idiotic responses. What is idiotic about a thread in which someone tries to get the opinion of users of a particular compound, in this case agmatine? Anyone that feels the thread is idiotic can let it be. If this individual decides to contribute in that thread, however, he should be ready for a healthy discussion, based on mutual respect, and should not refer to the others as "idiots" if they do not immediately share his apparently not-so-unshakeable "facts and science".
Well said. Reps to you sir.
 
BBB

BBB

Well-known member
Awards
1
  • Established
It does -- its a NMDA receptor antagonist in the body. You're gonna be swole and braindead :D

Seriously though, dont f*** with that stuff just to get a cool pump in the gym. Plenty of other things give you a pump without messing with your NMDA.

Plus, even in all the studies on agamatine, none of them talk about giving your body superphysiological levels of agamatine. None that I have seen at least. And even if there was, i highly doubt they tested how much NMDAreceptor was inhibited.

Just saying...use intelligence not bro'telligence. Science > supplement hype
Natty,

You need to do some more research. Doc Houser has a slide presentation that explains in intricate detail how this product works. NMDA concerns are not an issue.
 
DAdams91982

DAdams91982

Board Sponsor
Awards
2
  • RockStar
  • Established
AGREE 100%! We all can always learn, there is nothing wrong to state your argument, provide LEGIT reasoning and then answer/comment respectfully, its not hard. Problem is people have too much pride and arrogance and let that tragic flaw get the most out of themselves.
I am not in this thread, as I already made my mind up a long time ago that agamantine was dangerous and shouldn't be supplemented... BUT... Andrew your posts are pretty pointless. You seem to be the king of jumping in and agreeing with bull**** posts day in and day out. You are throwing stones when you are also at fault. I dont know how many posts that I have read of yours that only said 100% CORRECT.. when they were 100% WRONG.

Moral? Get off the high horse.
 
DAdams91982

DAdams91982

Board Sponsor
Awards
2
  • RockStar
  • Established
Natty,

You need to do some more research. Doc Houser has a slide presentation that explains in intricate detail how this product works. NMDA concerns are not an issue.
Can you provide his published study that is peer reviewed and accepted as fact? I would really like to see something accepted by the medical community to back up that assertion!
 
andrew732

andrew732

Well-known member
Awards
1
  • Established
I am not in this thread, as I already made my mind up a long time ago that agamantine was dangerous and shouldn't be supplemented... BUT... Andrew your posts are pretty pointless. You seem to be the king of jumping in and agreeing with bull**** posts day in and day out. You are throwing stones when you are also at fault. I dont know how many posts that I have read of yours that only said 100% CORRECT.. when they were 100% WRONG.

Moral? Get off the high horse.
Technically you are right because it is not always 100% true, it is MY OPINION on how I feel towards that subject manner. However if you want to bring up the heat I can. Personally, sometimes the things you say end up coming back to make you look bad. I feel you are a bit hypocritical on the way you carry yourself on these forums, just saying it as it is. I will not continue this conversation since it will lead no where and I will lose brain cells more than that of consuming some agamtine:eek:uttahere:. When you have more concrete evidence on agmatine I will hear you out, till then Carry on. :cheers:
 
DAdams91982

DAdams91982

Board Sponsor
Awards
2
  • RockStar
  • Established
Technically you are right because it is not always 100% true, it is MY OPINION on how I feel towards that subject manner. However if you want to bring up the heat I can. Personally, sometimes the things you say end up coming back to make you look bad. I feel you are a bit hypocritical on the way you carry yourself on these forums, just saying it as it is. I will not continue this conversation since it will lead no where and I will lose brain cells more than that of consuming some agamtine:eek:uttahere:. When you have more concrete evidence on agmatine I will hear you out, till then Carry on. :cheers:
If not buying into BS marketing makes me look bad, or hate on the idea of mislabeling product... then call me the Grinch.
 
andrew732

andrew732

Well-known member
Awards
1
  • Established
If not buying into BS marketing makes me look bad, or hate on the idea of mislabeling product... then call me the Grinch.
NOPE, not what I was implying but nothing new from you, so as I said before please carry on.:cheers:
 
DAdams91982

DAdams91982

Board Sponsor
Awards
2
  • RockStar
  • Established
NOPE, not what I was implying but nothing new from you, so as I said before please carry on.:cheers:
I would like to you to please chastize me and make me "look bad" in front of all. it is fine with me.

in the mean time:
(Please forgive the pull from wiki)
Agmatine ((4-aminobutyl)guanidine, NH2-CH2-CH2-CH2-CH2-NH-C(-NH2)(=NH)) is the decarboxylation product of the amino acid arginine and is an intermediate in polyamine biosynthesis. It is discussed as a putative neurotransmitter. It is synthesized in the brain, stored in synaptic vesicles, accumulated by uptake, released by membrane depolarization, and inactivated by agmatinase. Agmatine binds to α2-adrenergic receptor and imidazoline binding sites, and blocks NMDA receptors and other cation ligand-gated channels. Agmatine inhibits nitric oxide synthase (NOS), and induces the release of some peptide hormones.
Anyone who knows anything about the make up the brain chemistry and function will tell you supplementing agmatine is a bad idea and essentially dangerous. Not because what you think, but what is known about NMDA. With respect to Dr. Houser (Cause I do enjoy his information)... I have yet to see 1 study published by him that proves safety. I love my brain, been with me for life... something I do NOT want to jack with... a reason I say L-DOPA is dangerous as well. My liver can regenerate, and can be protected... not so much with my ability to remember.
 
BBB

BBB

Well-known member
Awards
1
  • Established
I would like to you to please chastize me and make me "look bad" in front of all. it is fine with me.

in the mean time:
(Please forgive the pull from wiki)


Anyone who knows anything about the make up the brain chemistry and function will tell you supplementing agmatine is a bad idea and essentially dangerous. Not because what you think, but what is known about NMDA. With respect to Dr. Houser (Cause I do enjoy his information)... I have yet to see 1 study published by him that proves safety. I love my brain, been with me for life... something I do NOT want to jack with... a reason I say L-DOPA is dangerous as well. My liver can regenerate, and can be protected... not so much with my ability to remember.
You may want to follow his research: http://www.*************/forum/articles/1271-agmatine-research-update-slide-show.html
 

Similar threads


Top